Selective inhibition of T cell responses by protein and peptide-based immunotherapy

Recent progress in understanding antigen presentation to T cells has permitted researchers to identify a number of suitable attack points for selective immunointervention aimed at inhibiting inappropriate T cell activation: major histocompatibility complex (MHC) molecules, T cell receptor (TCR), CD4/CD8, and other accessory molecules. This has fostered the development of a new generation of immunosuppressive agents potentially useful in the prevention and/or treatment of autoimmune diseases, and induction of selective immunosuppression is currently being attempted using monoclonal antibodies or synthetic peptides. The selective immunosuppression by proteins and peptides may be sub-divided into three major categories: i) passive treatments aimed at inhibiting T cell activation by blocking the MHC binding site to any antigenic peptide, including autoantigens; ii) treatments aimed at incapacitating the autoreactive T cells, either by administration of the candidate autoantigen as protein or peptides in tolerogenic form, or by TCR antagonists able to induce selective T cell anergy; and iii) vaccination-like treatments aimed at inducing or enhancing regulatory T cells able to control the activity of pathogenic, autoreactive T cell. It is hoped that some of these approaches may finally lead to effective treatments able to interfere with the induction and/or progression of human autoimmune diseases.